PMID:22053207

Citation	Zhou, H, Shen, DF, Bian, ZY, Zong, J, Deng, W, Zhang, Y, Guo, YY, Li, H and Tang, QZ (2011) Activating transcription factor 3 deficiency promotes cardiac hypertrophy, dysfunction, and fibrosis induced by pressure overload. PLoS ONE 6:e26744
Abstract	Activating transcription factor 3 (ATF3), which is encoded by an adaptive-response gene induced by various stimuli, plays an important role in the cardiovascular system. However, the effect of ATF3 on cardiac hypertrophy induced by a pathological stimulus has not been determined. Here, we investigated the effects of ATF3 deficiency on cardiac hypertrophy using in vitro and in vivo models. Aortic banding (AB) was performed to induce cardiac hypertrophy in mice. Cardiac hypertrophy was estimated by echocardiographic and hemodynamic measurements and by pathological and molecular analysis. ATF3 deficiency promoted cardiac hypertrophy, dysfunction and fibrosis after 4 weeks of AB compared to the wild type (WT) mice. Furthermore, enhanced activation of the MEK-ERK1/2 and JNK pathways was found in ATF3-knockout (KO) mice compared to WT mice. In vitro studies performed in cultured neonatal mouse cardiomyocytes confirmed that ATF3 deficiency promotes cardiomyocyte hypertrophy induced by angiotensin II, which was associated with the amplification of MEK-ERK1/2 and JNK signaling. Our results suggested that ATF3 plays a crucial role in the development of cardiac hypertrophy via negative regulation of the MEK-ERK1/2 and JNK pathways.
Links	PubMed PMC3203896 Online version:10.1371/journal.pone.0026744
Keywords	Activating Transcription Factor 3/deficiency; Activating Transcription Factor 3/metabolism; Animals; Cardiomegaly/complications; Cardiomegaly/metabolism; Cardiomegaly/pathology; Cardiomegaly/physiopathology; Cardiomyopathy, Dilated/complications; Cardiomyopathy, Dilated/metabolism; Cardiomyopathy, Dilated/pathology; Cardiomyopathy, Dilated/physiopathology; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases/metabolism; Fibrosis; Hemodynamics; Humans; JNK Mitogen-Activated Protein Kinases/metabolism; MAP Kinase Signaling System; Male; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase Kinases/metabolism; Myocardium/enzymology; Myocardium/pathology; Myocytes, Cardiac/metabolism; Myocytes, Cardiac/pathology; Ventricular Pressure
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:ATF3		GO:0070373: negative regulation of ERK1 and ERK2 cascade	ECO:0000315:		P		Figure 4 shows the relative protein levels of proteins produced in the ERK cascade after the ATF3 gene has been knocked out as compared to the wild type gene expression.	complete CACAO 4903
MOUSE:ATF3	involved_in	GO:0070373: negative regulation of ERK1 and ERK2 cascade	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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